Mechanisms of the proteinuria induced by Rho GTPases

Liming Wang, Mathew J. Ellis, Jose A. Gomez, William Eisner, Walter Fennell, David N. Howell, Phillip Ruiz, Timothy A. Fields, Robert F. Spurney

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively active (V14 Rho) or dominant-negative Rho A (N19 Rho) in podocytes. Specific induction of either Rho A construct in podocytes caused albuminuria and foot process effacement along with disruption of the actin cytoskeleton as evidenced by decreased expression of the actin-associated protein synaptopodin. The mechanisms of these adverse effects, however, appeared to be different. Active V14 Rho enhanced actin polymerization, caused a reduction in nephrin mRNA and protein levels, promoted podocyte apoptosis, and decreased endogenous Rho A levels. In contrast, the dominant-negative N19 Rho caused a loss of podocyte stress fibers, did not alter the expression of either nephrin or Rho A, and did not cause podocyte apoptosis. Thus, our findings suggest that Rho A plays an important role in maintaining the integrity of the glomerular filtration barrier under basal conditions, but enhancement of Rho A activity above basal levels promotes podocyte injury.

Original languageEnglish
Pages (from-to)1075-1085
Number of pages11
JournalKidney International
Volume81
Issue number11
DOIs
StatePublished - Jun 1 2012

Fingerprint

Podocytes
rho GTP-Binding Proteins
Proteinuria
Glomerular Filtration Barrier
Actins
Apoptosis
Stress Fibers
Proteins
Albuminuria
Monomeric GTP-Binding Proteins
Doxycycline
Actin Cytoskeleton
Polymerization
Transgenic Mice
Foot
Messenger RNA
Wounds and Injuries

Keywords

  • cell signaling
  • glomerular disease
  • podocyte

ASJC Scopus subject areas

  • Nephrology

Cite this

Wang, L., Ellis, M. J., Gomez, J. A., Eisner, W., Fennell, W., Howell, D. N., ... Spurney, R. F. (2012). Mechanisms of the proteinuria induced by Rho GTPases. Kidney International, 81(11), 1075-1085. https://doi.org/10.1038/ki.2011.472

Mechanisms of the proteinuria induced by Rho GTPases. / Wang, Liming; Ellis, Mathew J.; Gomez, Jose A.; Eisner, William; Fennell, Walter; Howell, David N.; Ruiz, Phillip; Fields, Timothy A.; Spurney, Robert F.

In: Kidney International, Vol. 81, No. 11, 01.06.2012, p. 1075-1085.

Research output: Contribution to journalArticle

Wang, L, Ellis, MJ, Gomez, JA, Eisner, W, Fennell, W, Howell, DN, Ruiz, P, Fields, TA & Spurney, RF 2012, 'Mechanisms of the proteinuria induced by Rho GTPases', Kidney International, vol. 81, no. 11, pp. 1075-1085. https://doi.org/10.1038/ki.2011.472
Wang L, Ellis MJ, Gomez JA, Eisner W, Fennell W, Howell DN et al. Mechanisms of the proteinuria induced by Rho GTPases. Kidney International. 2012 Jun 1;81(11):1075-1085. https://doi.org/10.1038/ki.2011.472
Wang, Liming ; Ellis, Mathew J. ; Gomez, Jose A. ; Eisner, William ; Fennell, Walter ; Howell, David N. ; Ruiz, Phillip ; Fields, Timothy A. ; Spurney, Robert F. / Mechanisms of the proteinuria induced by Rho GTPases. In: Kidney International. 2012 ; Vol. 81, No. 11. pp. 1075-1085.
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